scholarly journals Analysis of genes and underlying mechanisms involved in foam cells formation and atherosclerosis development

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10336
Author(s):  
Kai Zhang ◽  
Xianyu Qin ◽  
Xianwu Zhou ◽  
Jianrong Zhou ◽  
Pengju Wen ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Biological Process ◽  
Foam Cells ◽  
Significant Difference ◽  
The Common ◽  
Atherosclerosis Development ◽  
Underlying Mechanisms ◽  
Pathway Analyses ◽  
Atherosclerosis Treatment ◽  
Gene Ontology Biological Process

Background Foam cells (FCs) play crucial roles in the process of all stages of atherosclerosis. Smooth muscle cells (SMCs) and macrophages are the major sources of FCs. This study aimed to identify the common molecular mechanism in these two types of FCs. Methods GSE28829, GSE43292, GSE68021, and GSE54666 were included to identify the differentially expressed genes (DEGs) associated with FCs derived from SMCs and macrophages. Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using the DAVID database. The co-regulated genes associated with the two origins of FCs were validated (GSE9874), and their expression in vulnerable atherosclerosis plaques (GSE120521 and GSE41571) was assessed. Results A total of 432 genes associated with FCs derived from SMCs (SMC-FCs) and 81 genes associated with FCs derived from macrophages (M-FCs) were identified, and they were mainly involved in lipid metabolism, inflammation, cell cycle/apoptosis. Furthermore, three co-regulated genes associated with FCs were identified: GLRX, RNF13, and ABCA1. These three common genes showed an increased tendency in unstable or ruptured plaques, although in some cases, no statistically significant difference was found. Conclusions DEGs related to FCs derived from SMCs and macrophages have contributed to the understanding of the molecular mechanism underlying the formation of FCs and atherosclerosis. GLRX, RNF13, and ABCA1 might be potential targets for atherosclerosis treatment.

scholarly journals DARAPLADIB INHIBIT ADHESION MOLECULE EXPRESSION IN AORTA AT EARLY STAGES OF ATHEROSCLEROSIS USING SPRAGUE-DAWLEY TYPE 2 DIABETES MELLITUS MODEL

2017 ◽  
Vol 10 (6) ◽  
pp. 373 ◽  
Author(s):  
Heriansyah T ◽  
Hanifa H ◽  
Andarini S ◽  
Wihastuti Titin Andri
Keyword(s):  
Diabetes Mellitus ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Fasting Blood Glucose ◽  
Sprague Dawley ◽  
Nonesterified Fatty Acids ◽  
Early Stages ◽  
Significant Difference ◽  
Atherosclerosis Treatment

Objective: Hyperglycemia and hyperlipidemia in diabetes mellitus (DM) can lead an atherosclerosis. The increase of low-density lipoprotein level in DM and atherosclerosis is correlated with lipoprotein-associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids. LysoPC regulated inflammation mediators, include cytokines, adhesion molecules (such as vascular cell adhesion molecule-1 [VCAM-1] and intercellular adhesion molecules-1 [ICAM-1]), and monocyte chemoattractant protein-1 (MCP-1) chemotactic. Darapladib is known as a Lp-PLA2 specific inhibitor. It is also considered to be an atherosclerosis treatment. The aim of this study is to know darapladib effect on VCAM-1 and ICAM-1 aorta expression in early stages of atherosclerosis using Sprague-Dawley Type 2 DM (T2DM) model.Methods: About 30 Spraque-Dawley rats are divided into three main groups: Normal, T2DM, and T2DM with darapladib administration group. Each group consists of 2 serials treatment time: 8 and 16 weeks treatment group. Fasting blood glucose, resistance insulin, and lipid profile were measured and analyzed to ensure T2DM model. VCAM-1 and ICAM-1 expression were measured using double staining immunofluorescence. Each data were analyzed using one-way ANOVA.Results: There is a significant difference in VCAM-1 expression in T2DM group (8 and 16 weeks), with p=0.011 and 0.034 (p<0.05), respectively. Mean while, a significant difference for ICAM-1 only showed in 8 weeks T2DM group with p=0.03 (p<0.05). Moreover, there is a decreasing trend in 16 weeks T2DM group.Conclusion: Our results showed that darapladib can decrease VCAM-1 and ICAM-1 aorta expression in early stages of atherosclerosis using Sprague- Dawley T2DM model. This showed another evidence of darapladib as atherosclerosis treatment.

scholarly journals Heparan Sulfate Deficiency in Cartilage: Enhanced BMP-Sensitivity, Proteoglycan Production and an Anti-Apoptotic Expression Signature after Loading

2021 ◽  
Vol 22 (7) ◽  
pp. 3726
Author(s):  
Matthias Gerstner ◽  
Ann-Christine Severmann ◽  
Safak Chasan ◽  
Andrea Vortkamp ◽  
Wiltrud Richter
Keyword(s):  
Heparan Sulfate ◽  
Pain Perception ◽  
Biological Process ◽  
Transcriptome Profiling ◽  
Mrna Levels ◽  
Unconfined Compression ◽  
Expression Signature ◽  
Hypomorphic Allele ◽  
Underlying Mechanisms ◽  
Engineered Cartilage

Osteoarthritis (OA) represents one major cause of disability worldwide still evading efficient pharmacological or cellular therapies. Severe degeneration of extracellular cartilage matrix precedes the loss of mobility and disabling pain perception in affected joints. Recent studies showed that a reduced heparan sulfate (HS) content protects cartilage from degradation in OA-animal models of joint destabilization but the underlying mechanisms remained unclear. We aimed to clarify whether low HS-content alters the mechano-response of chondrocytes and to uncover pathways relevant for HS-related chondro-protection in response to loading. Tissue-engineered cartilage with HS-deficiency was generated from rib chondrocytes of mice carrying a hypomorphic allele of Exostosin 1 (Ext1), one of the main HS-synthesizing enzymes, and wildtype (WT) littermate controls. Engineered cartilage matured for 2 weeks was exposed to cyclic unconfined compression in a bioreactor. The molecular loading response was determined by transcriptome profiling, bioinformatic data processing, and qPCR. HS-deficient chondrocytes expressed 3–6% of WT Ext1-mRNA levels. Both groups similarly raised Sox9, Col2a1, and Acan levels during maturation. However, HS-deficient chondrocytes synthesized and deposited 50% more GAG/DNA. TGFβ and FGF2-sensitivity of Ext1gt/gt chondrocytes was similar to WT cells but their response to BMP-stimulation was enhanced. Loading induced similar activation of mechano-sensitive ERK and P38-signaling in WT and HS-reduced chondrocytes. Transcriptome analysis reflected regulation of cell migration as major load-induced biological process with similar stimulation of common (Fosl1, Itgα5, Timp1, and Ngf) as well as novel mechano-regulated genes (Inhba and Dhrs9). Remarkably, only Ext1-hypomorphic cartilage responded to loading by an expression signature of negative regulation of apoptosis with pro-apoptotic Bnip3 being selectively down-regulated. HS-deficiency enhanced BMP-sensitivity, GAG-production and fostered an anti-apoptotic expression signature after loading, all of which may protect cartilage from load-induced erosion.

Lactobacillus casei LC89 exert antidiabetic effects through regulating hepatic glucagon response and gut microbiota in type 2 diabetic mice

2021 ◽  
Author(s):  
Yongli Zhang ◽  
Tao Wu ◽  
Wen Li ◽  
Yunjiao Zhao ◽  
Hairong Long ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Molecular Mechanism ◽  
Lactobacillus Casei ◽  
Diabetic Mice ◽  
Antihyperglycemic Activity ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic ◽  
Antidiabetic Effects

Previous study suggests Lactobacillus casei exhibit antihyperglycemic activity, however, the molecular mechanism has rarely been elucidated. Here, the anti-diabetic effects and underlying mechanisms of Lactobacillus casei LC89 were investigated in...

scholarly journals PGC7 suppresses TET3 for protecting DNA methylation

2013 ◽  
Vol 42 (5) ◽  
pp. 2893-2905 ◽  
Author(s):  
Chunjing Bian ◽  
Xiaochun Yu
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanism ◽  
Biological Process ◽  
Cpg Islands ◽  
Binding Motifs ◽  
Genome Wide Analysis ◽  
Dna Motif ◽  
Genome Wide

Abstract Ten-eleven translocation (TET) family enzymes convert 5-methylcytosine to 5-hydroxylmethylcytosine. However, the molecular mechanism that regulates this biological process is not clear. Here, we show the evidence that PGC7 (also known as Dppa3 or Stella) interacts with TET2 and TET3 both in vitro and in vivo to suppress the enzymatic activity of TET2 and TET3. Moreover, lacking PGC7 induces the loss of DNA methylation at imprinting loci. Genome-wide analysis of PGC7 reveals a consensus DNA motif that is recognized by PGC7. The CpG islands surrounding the PGC7-binding motifs are hypermethylated. Taken together, our study demonstrates a molecular mechanism by which PGC7 protects DNA methylation from TET family enzyme-dependent oxidation.

INCIDENCE OF CRANIAL NERVE PARALYSIS IN POLIOMYELITIS IN RELATION TO PRESENCE OR ABSENCE OF TONSILS

PEDIATRICS ◽  
1958 ◽  
Vol 21 (1) ◽  
pp. 94-105
Author(s):  
F. H. Top
Keyword(s):  
Facial Nerve ◽  
Cranial Nerves ◽  
Age Group ◽  
Real Difference ◽  
Satisfactory Explanation ◽  
Nerve Paralysis ◽  
Cranial Nerve Paralysis ◽  
Significant Difference ◽  
The Central Nervous System ◽  
The Common

Evidence is presented from data covering the period 1940 to 1952 which corroborates the conclusion of previous studies that prior tonsillectomy probably adversely affects the occurrence of brainstem paralysis (bulbar and bulbospinal) in poliomyelitis. Neither this study nor any preceding studies relating to this problem have proved the contention. On the basis that the hypothesis is correct, an attempt is made to find an answer by studying the incidence of the common paralysis of cranial nerves (VII, IX and X and XI) in bulbar and bulbospinal cases of poliomyelitis on the basis of presence or absence of tonsils. Rates of incidence of paralysis of cranial nerves, not adjusted for age, indicate a decidedly higher proportion of paralysis of the facial nerve (VII) among nontonsillectomized patients whereas tonsillectomized persons are preportionately more affected by palatal and pharyngeal paralysis (nerves IX and X). Paralysis of the facial nerve appears from two studies to occur more commonly at earlier ages, particularly in the age group 0 to 4 years. However, age adjustment did not erase, although it did somewhat lower, the TR/TP ratio. This finding lends credence to a real difference but can only be applied to this study, as Paffenbarger in a smaller study found no significant difference in frequencies of paralysis of the facial nerve between groups with tonsils removed and tonsils present, and Southcott, also in a small study, found paralysis of the facial nerve more common among tonsillectomized patients with bulbar (includes bulbospinal) involvement. The differences noted for palatal and pharyngeal paralyses (nerves IX and X) in the unadjusted rates as between tonsillectomized and nontonsillectomized patients remain statistically different and in some instances significant when corrections for age are made. The results of this study are suggestive but give no entirely satisfactory explanation for the differences noted. Various explanations previously offered are cited and briefly discussed. Perhaps more definitive studies in animals along the approach suggested by Southcott will prove more fruitful, namely, labelling virus by some radioactive element in order to trace the route it takes to the central nervous system.

Correlation Between Intestinal Microflora and Gastrointestinal Dysfunction in Elderly Patients with Sepsis

2020 ◽  
Vol 12 (8) ◽  
pp. 1030-1037
Author(s):  
Hailing Yang ◽  
Xiaolin Zhang ◽  
Weijun Chen ◽  
Libo Shang ◽  
Bin Chen ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Intestinal Microflora ◽  
Sepsis Group ◽  
Control Group ◽  
Gastrointestinal Dysfunction ◽  
E Coli ◽  
Significant Difference ◽  
Prevention And Treatment ◽  
The Common ◽  
Wbc Count

Multiple organ dysfunction syndrome (MODS) is a key factor that leads to death in elderly patients with sepsis. Therefore, early prevention and treatment of gastrointestinal dysfunction (GIDF) in elderly patients with sepsis is an important measure to prevent MODS occurrence. This research explores the correlation between intestinal microflora and GIDF in elderly patients with sepsis and provides ideas for the prevention and treatment of GIDF in elderly patients with sepsis. In this study, 152 patients with sepsis (122 patients with sepsis and GIDF) treated in the Third Affiliated Hospital of Yunnan University of Chinese Medicine from January to September 2019 were selected as the sepsis group and 100 elderly who had normal physical examination results were selected as the control group. The common intestinal microflora of the two groups was compared. Patients with sepsis and GIDF were treated as the GIDF group and the other patients with sepsis were treated as the non-GIDF group. The common intestinal microflora, gastrointestinal indicators, serum inflammatory factors, and immune function indices were compared between the two groups. Correlation analysis of the observed indices with statistical significance was carried out. The results showed 152 patients with sepsis and 122 patients with sepsis and GIDF; thus, the incidence of sepsis with GIDF was 80.26%. The total average score of sepsis with GIDF was 3.61±0.09. There was no statistically significant difference in GIDF scores of patients ages 65–75 and > 75 years old. The number of Bifidobacterium and Lactobacillus in elderly patients with sepsis was lower and the number of Escherichia coli was higher than in the control group. In elderly patients with sepsis, the number of Bifidobacterium and Lactobacillus in the GIDF group was lower and the number of E. coli was higher than in the non-GIDF group. White blood cell (WBC) count, procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), gastrin (GAS), and diamine oxidase (DAO) in GIDF patients were higher and motilin (MOT), CIT (CIT), CD4+, and CD8+ were lower than in the non-GIDF group. WBC count, PCT, CRP, TNF-α, GAS, and DAO were negatively correlated with the number of Bifidobacterium and Lactobacillus but positively correlated with E. coli. MOT, CIT, CD4+, and CD8+ were positively correlated with the number of Bifidobacterium and Lactobacillus but negatively correlated with E. coli. There was a negative correlation between Bifidobacterium and Lactobacillus and GIDF score and a positive correlation between E. coli and GIDF score. Therefore, the change in the intestinal microflora in elderly patients with sepsis is related to GIDF.

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